Ameliorative effects of the Coptis inflorescence extract against lung injury in diabetic mice by regulating AMPK/NEU1 signaling.

BACKGROUND: In diabetic patients, complications are the leading cause of death and disability, while diabetic lung damage has received little research. The Coptis inflorescence extract (CE) has hypoglycemic properties, but the mechanism of its protective role on diabetic lung injury is understood. PURPOSE: This study aims to explore the protective actions and molecular mechanism of CE and its active ingredients in diabetic lung disease. METHOD: Twenty-nine metabolites were identified in the metabolomic profile of CE using HPLC-ESI/MS, and high-content substances of berberine (BBR) and linarin (LIN) were isolated from CE using column chromatography. The potential targets and molecular mechanisms of CE against diabetic lung damage were systematically investigated by network pharmacology and in vitro experimental validation. RESULTS: CE significantly improved lung function and pathology. CE (360 mg/kg) or metformin treatment significantly improved lipid metabolism disorders, including decreased HDL-C and elevated serum TG, TC, and LDL-C levels. Furthermore, CE's chemical composition was determined using the HPLC-QTOF-MS method. CE identified five compounds as candidate active compounds (Berberine, Linarin, Palmatine, Worenine, and Coptisine). Network pharmacology analysis predicted CE contained five active compounds and target proteins, that AMPK, TGFß1, and Smad might be the key targets in treating diabetic lung injury. Then we investigated the therapeutic effect of bioactive compounds of CE on diabetic lung damage through in vivo and in vitro experiments. Intragastric administration with BBR (50 mg/kg) or LIN (20 mg/kg) suppressed weight loss, hyperglycemia, and dyslipidemia, significantly alleviating lung inflammation in diabetic mice. Further mechanism research revealed that LIN or BBR inhibited alveolar epithelial-mesenchymal transition induced by high glucose by regulating AMPK/NEU-mediated signaling pathway. CONCLUSION: In conclusion, the administration of CE can effectively alleviate diabetic lung damage, providing a scientific basis for lowering blood sugar to moisturize lung function. BBR and LIN, the main components of CE, can effectively alleviate diabetic lung damage by regulating AMPK/NEU1 Signaling and inhibiting the TGF-ß1 level, which may be a critical mechanism of its effects.

[Bivariate statistical model for calculating phosphorus input loads to the river from point and nonpoint sources].

Based on the hydrological difference between the point source (PS) and nonpoint source (NPS) pollution processes and the major influencing mechanism of in-stream retention processes, a bivariate statistical model was developed for relating river phosphorus load to river water flow rate and temperature. Using the calibrated and validated four model coefficients from in-stream monitoring data, monthly phosphorus input loads to the river from PS and NPS can be easily determined by the model. Compared to current hydrologica methods, this model takes the in-stream retention process and the upstream inflow term into consideration; thus it improves the knowledge on phosphorus pollution processes and can meet the requirements of both the district-based and watershed-based wate quality management patterns. Using this model, total phosphorus (TP) input load to the Changle River in Zhejiang Province was calculated. Results indicated that annual total TP input load was (54.6 +/- 11.9) t x a(-1) in 2004-2009, with upstream water inflow, PS and NPS contributing to 5% +/- 1%, 12% +/- 3% and 83% +/- 3%, respectively. The cumulative NPS TP input load during the high flow periods (i. e. , June, July, August and September) in summer accounted for 50% +/- 9% of the annual amount, increasing the alga blooming risk in downstream water bodies. Annual in-stream TP retention load was (4.5 +/- 0.1) t x a(-1) and occupied 9% +/- 2% of the total input load. The cumulative in-stream TP retention load during the summer periods (i. e. , June-September) accounted for 55% +/- 2% of the annual amount, indicating that in-stream retention function plays an important role in seasonal TP transport and transformation processes. This bivariate statistical model only requires commonly available in-stream monitoring data (i. e. , river phosphorus load, water flow rate and temperature) with no requirement of special software knowledge; thus it offers researchers an managers with a cost-effective tool for quantifying TP pollution processes in both district and watershed scales.

Atomic force microscopy investigation of the giant mimivirus.

Mimivirus was investigated by atomic force microscopy in its native state following serial degradation by lysozyme and bromelain. The 750-nm diameter virus is coated with a forest of glycosylated protein fibers of lengths about 140 nm with diameters 1.4 nm. Fibers are capped with distinctive ellipsoidal protein heads of estimated Mr=25 kDa. The surface fibers are attached to the particle through a layer of protein covering the capsid, which is in turn composed of the major capsid protein (MCP). The latter is organized as an open network of hexagonal rings with central depressions separated by 14 nm. The virion exhibits an elaborate apparatus at a unique vertex, visible as a star shaped depression on native particles, but on defibered virions as five arms of 50 nm width and 250 nm length rising above the capsid by 20 nm. The apparatus is integrated into the capsid and not applied atop the icosahedral lattice. Prior to DNA release, the arms of the star disengage from the virion and it opens by folding back five adjacent triangular faces. A membrane sac containing the DNA emerges from the capsid in preparation for fusion with a membrane of the host cell. Also observed from disrupted virions were masses of distinctive fibers of diameter about 1 nm, and having a 7-nm periodicity. These are probably contained within the capsid along with the DNA bearing sac. The fibers were occasionally observed associated with toroidal protein clusters interpreted as processive enzymes modifying the fibers.